AIPL1

Chr 17ADAR

AIP like 1 HSP90 co-chaperone

Also known as: AIPL2, LCA4

NCBI Gene: 23746ENSG00000129221UniProt: Q9NZN9OMIM: 604392

AIPL1 encodes aryl-hydrocarbon interacting protein-like 1, which functions as a chaperone protein important in protein trafficking, folding and stabilization in photoreceptor cells. Mutations cause autosomal recessive Leber congenital amaurosis with onset at birth or in the first few months of life (accounting for approximately 20% of cases), as well as autosomal dominant cone-rod dystrophy and juvenile retinitis pigmentosa. The gene shows low constraint against loss-of-function variants (pLI <0.001), consistent with recessive inheritance being the primary disease mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 1.073 OMIM phenotypes
Clinical Summary— AIPL1
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Gene-Disease Validity (ClinGen)
AIPL1-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 141 VUS of 441 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — AIPL1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.37
OE 0.63 (0.39–1.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.08Z-score
OE missense 0.99 (0.89–1.10)
235 obs / 238.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.63 (0.39–1.07)
0≤0.351.4
Missense OE0.99 (0.89–1.10)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 10 / 15.9Missense obs/exp: 235 / 238.4Syn Z: 0.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAIPL1-related Leber congenital amaurosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6744th %ile
GOF
0.75top 25%
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

441 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic24
VUS141
Likely Benign178
Benign16
Conflicting24
50
Pathogenic
24
Likely Pathogenic
141
VUS
178
Likely Benign
16
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
7
22
0
50
Likely Pathogenic
8
11
5
0
24
VUS
4
92
40
5
141
Likely Benign
0
7
63
108
178
Benign
0
11
3
2
16
Conflicting
—24
Total33128133115433

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AIPL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Molecular Characterization of AIPL1-Associated Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy.
Zhang Q et al.·Am J Ophthalmol
2024
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
Georgiou M et al.·Prog Retin Eye Res
2024Review
Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study.
Michaelides M et al.·Lancet
2025
Gene and Cell Therapy for AIPL1-Associated Leber Congenital Amaurosis: Challenges and Prospects.
Perdigao PRL et al.·Adv Exp Med Biol
2019Review
Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy.
Xu K et al.·Br J Ophthalmol
2020Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients